MSK – Muscle

Master answer

Sarcomere

“Sarcomere” → basic unit of muscle contraction within myofibril

Components of the sarcomere:

• Myosin
  • Large protein that consists of:
    • 1x long tail – 2 interwound α-helices with a flexible hinge (S2 segment)
    • 2x globular heads (S1 segment) – Connected to long tail via S2 segment. Each head has 1x heavy chain that binds 1x G-actin, and 2x short chains that bind ATP
  • 2x myosins fuse together at M-line via their long tails → forms “thick filament”
• Actin (thin filament)
  • Consists of 2x chains of F-actin (≈ double-strand cord) formed from the polymerisation of G-actin
• Tropomyosin
  • 2x α-helical chains that lie between 2x chains of actin polymers → under the influence of Troponin, it can acts to inhibit or permit myosin-actin interaction
• Troponin
  • Present with tropomyosin on thin filament at regular intervals (every 7 actin monomers)
  • Consists of 3 subunits – (a) T (binds tropomyosin), (b) I (inhibits myosin ATPase) and (c) C (binds Ca2+)
  • Binding to Ca2+ causes a conformation change in troponin-tropomyosin complex → allows actin to interact with myosin
• Titin
  • Large elastic molecule that attaches myosin to Z-line → acts to return muscle to
    resting length

Process of Muscle Contraction and Relaxation:

(1) Excitation-contraction coupling:

• Motor neuron depolarisation
• ACh vesicular release
• Multiple MEPs → End plate potential
• Muscle AP propagates via T-tubles
• Opens L-type Ca channels
• Calcium induced calcium release from SR
• Ca-troponin C interaction
• Alteration and movement of Trop-tropomyocin complex
• Exposure of Actin
• Removal of Troponin I inhibition of myosin ATPase
• Cross bridge cycling

2) Contraction (Sliding filament cross bridge cycling):

• “Flexed” Myosin without ATP binds to Actin.
• Binding of ATP to Myosin causes release of Actin/Myosin complex and extension of the head
• In the presence of Ca, Actin binding sites are open and binding of myosin/Actin/ATP complex is formed
• Hydrolysis of ATP to ADP + P in myosin head causes a conformational change “initial flexing” the myosin head and releasing phosphate
• Release of ADP further flexes Myosin head
• In presence of Ca return to step 2

(3) Muscle relaxation:

1. AChE metabolises ACh in the NMJ → ↓ nAChR activation at MEP → ↓ EPP and muscle AP generation
2. SR actively sequesters Ca2+ (via Ca2+-Mg2+ ATPase) → ↓ IC [Ca2+] → Ca2+ removed from troponin C → tropomyosin mediated inhibition of actin-myosin interaction returns
3. Elastic components of the sarcomere causing the muscle to return to its normal length

Energy Source for Muscle Contraction

• Energy (in the form of ATP) is needed for muscle contraction AND relaxation
• The method of ATP generation depends on the level of activity present:
  • Creatinine phosphate store
    • ATP generated from Creatine phosphate during intense exercise
    • ADP + Creatine phosphate → ATP + creatinine (enzyme: Creatine Phosphokinase)
    • Replenished at rest by reversing the above reaction by aerobic/anaerobic generation of ATP
  • Aerobic generation of ATP:
    • Glucose (and Glycogen stores) – ATP is produced during exercise/activity by substrate phosphorylation (via glycolysis) and oxidative phosphorylation (via Kreb’s cycle and the ETC)
    • Fat – β-oxidation of fat produces ATP during light exercise and at rest
  • Anaerobic generation of ATP:
    • When O2 supplies are insufficient, ATP is produced in smaller amounts from the anaerobic glycolysis of glucose → produces lactic acid

JC / Gladwin 2020

Answer by Gladwin, JC